The objectives of the present study are: 1) to identify, study the ultrastructure and determine the origin of corneal presumptive free nerve endings, and 2) to determine the central (brainstem) termination sites and synaptic connections of known corneal sensory neurons. In the first series of experiments, the tracer horseradish peroxidase (HRP) will be injected into either the trigeminal or superior cervical ganglia of adult rats. The enzyme will be endocytosed by the ganglion cell bodies and transported intraaxonally to the corneal nerve terminals. The HRP-labelled corneal nerve endings will be identified at the electron microscopic level and analyzed critically with reference to their respective origins, ultrastructures, modes of termination, and peripheral distributions. In the second series of experiments, corneas from untreated rats and rats subjectd to 15 minutes of continuous unilateral corneal stimulation immediately prior to sacrifice, will be processed for substance P immunocytochemistry. The tissue will be stained according to the peroxidase-anti-peroxidase method of Sternberger and examined with the electron microscope. The material will be analyzed to determine if substance P is associated with any special organelle within corneal nerve endings, and to determine if there is any morphological evidence for substance P release from corneal nerve endings following prolonged corneal stimulation. In the final set of experiments, the central projections of trigeminal primary afferent neurons that innervate the cornea will be determined experimentally by the method of transganglionic transport of HRP. The distribution, ultrastructure, and synaptic relationships of the centrally directed corneal afferent fibers will be identified and analyzed. The results of the present study should increase significantly our understanding of the nature, source, and possible functions of the corneal innervation, and of the anatomical substrates that underlie the peripheral and central neural mechanisms of corneal sensibility.